Mixed Effects Research Articles

Population pharmacokinetics and dose rationale for aciclovir in term and pre-term neonates with herpes.

Aciclovir is considered the first-line treatment against Herpes simplex virus (HSV) infections in new-borns and infants. As renal excretion is the major route of elimination, in renally-impaired patients, aciclovir doses are adjusted according to the degree of impairment. However, limited attention has been given to the implications of immature renal function or dysfunction due to the viral disease itself. The aim of this investigation was to characterize the pharmacokinetics of aciclovir taking into account maturation and disease processes in the neonatal population. Pharmacokinetic data obtained from 2 previously published clinical trials (n = 28) were analyzed using a nonlinear mixed effects modeling approach. Post-menstrual age (PMA) and creatinine clearance (CLCR) were assessed as descriptors of maturation and renal function. Simulation scenarios were also implemented to illustrate the use of pharmacokinetic data to extrapolate efficacy from adults. Aciclovir pharmacokinetics was described by a one-compartment model with first-order elimination. Body weight and diagnosis (systemic infection) were statistically significant covariates on the volume of distribution, whereas body weight, CLCR and PMA had a significant effect on clearance. Median clearance varied from 0.2 to 1.0 L/h in subjects with PMA <34 or ≥34 weeks, respectively. Population estimate for volume of distribution was 1.93 L with systemic infection increasing this value by almost 3-fold (2.67 times higher). A suitable model parameterization was identified, which discriminates the effects of developmental growth, maturation, and organ function. Exposure to aciclovir was found to increase with decreasing PMA and renal function (CLCR), suggesting different dosing requirement for pre-term neonates.

Mental health after the COVID-19 pandemic among Finnish youth: a repeated, cross-sectional, population-based study

High levels of mental health problems among young people were reported during the COVID-19 pandemic, but studies of the post-pandemic period are scarce. We assessed mental health problems among Finnish youth before, during, and after the COVID-19 pandemic using nationwide population-based samples. Our aim was to examine in which direction the heightened levels of adolescent mental health problems have developed after the pandemic. In this national, repeated cross-sectional, population-based study in Finland, we recruited students at lower and upper secondary level (aged 13-20 years) who were taking part in the Finnish School Health Promotion (SHP) survey in 2015-23 (119 681-158 897 participants per round). The SHP is based on total sampling and conducted biennially between March and May. Self-reports covered the seven-item Generalized Anxiety Disorder Scale; the two-item Patient Health Questionnaire for depression; the Mini Social Phobia Inventory for social anxiety; the Short Warwick-Edinburgh Mental Wellbeing Scale for mental wellbeing; loneliness; the Sick, Control, One Stone, Fat, Food measure for disordered eating; and suicidality (suicidal ideation, deliberate self-harm, and suicide attempts). Scales were dichotomised using validated cutoffs. Presence of any and comorbid mental health problems was assessed. Logistic (for dichotomised outcomes) and linear (for Short Warwick-Edinburgh Mental Wellbeing Scale) mixed effects models were used to analyse the effect of survey year on mental health, controlling for sociodemographic background factors and stratified by gender and school level. Cisgender and transgender youth were compared. Between 2015 and 2023, the SHP study recruited 722 488 students (371 634 [51·6%] girls and 348 857 [48·4%] boys) with a mean age of 15·8 years (SD 1·3) who were either in the eighth and ninth grades of comprehensive school or the first and second years of general and vocational upper secondary schools in Finland. The proportion of participants with generalised anxiety, depression, and social anxiety symptoms above the cutoff increased from pre-COVID-19 levels to 2021 and remained at these higher levels in 2023 among all study groups. Among girls in lower secondary education, prevalence of generalised anxiety, depression, and social anxiety symptoms increased from 2021 to 2023, as did social anxiety among girls in upper secondary education. Among boys, the proportion with social anxiety symptoms decreased between 2021 and 2023. Mental wellbeing scores decreased in all groups between 2021 and 2023, and disordered eating increased in girls, and in boys in lower secondary education. Suicidality increased in girls but not in boys. Loneliness was the only measure to show improvement in all groups from 2021 to 2023. In 2023, 55 895 (72·6%) of 76 994 girls and 22 718 (32·8%) of 69 205 boys reported at least one mental health problem, and 37 250 (48·4%) girls and 9442 (13·6%) boys reported comorbid mental health problems. Among both transfeminine and transmasculine youth, the prevalence of generalised anxiety and depression symptoms decreased from 2021 to 2023, but compared with cisgender youth, the proportions were significantly higher throughout. The effects of the COVID-19 pandemic on youth mental health could be long lasting. In this study, the substantial change for the better among transgender youth was a positive exception. Providing adequate support and treatment for young people with poor mental health is essential, but solutions to the mental health crisis need to address a wider societal perspective and should be developed in partnership with young people. NordForsk, Research Council of Finland. For the Finnish and Swedish translations of the abstract see Supplementary Materials section.

Effects of a ketogenic diet on motor function and motor unit number estimation in aged C57BL/6 mice

ObjectivePathological, age-related loss of muscle function, commonly referred to as sarcopenia, contributes to loss of mobility, impaired independence, as well as increased risk of adverse health events. Sarcopenia has been attributed to changes in both neural and muscular integrity during aging. Current treatment options are primarily limited to exercise and dietary protein fortification, but the therapeutic impact of these approaches are often inadequate. Prior work has suggested that a ketogenic diet (KD) might improve healthspan and lifespan in aging mice. Thus, we sought to investigate the effects of a KD on neuromuscular indices of sarcopenia in aged C57BL/6 mice. DesignA randomized, controlled pre-clinical experiment consisting of longitudinal assessments performed starting at 22-months of age (baseline) as well as 2, 6 and 10 weeks after the start of a KD vs. regular chow intervention. SettingPreclinical laboratory study. Sample sizeThirty-six 22-month-old mice were randomized into 2 dietary groups: KD [n = 22 (13 female and 9 male)], and regular chow [n = 15 (7 female and 8 male)]. MeasurementsMeasures included body mass, hindlimb and all limb grip strength, rotarod for motor performance, plantarflexion muscle contractility, motor unit number estimations (MUNE), and repetitive nerve stimulation (RNS) as an index of neuromuscular junction transmission efficacy recorded from the gastrocnemius muscle. At end point, muscle wet weight and blood samples were collected to assess blood beta-hydroxybutyrate levels. Statistical analysisPrimary analyses were two-way mixed effects ANOVA (diet and time × diet) to determine the effect of a KD on indices of motor function (grip, rotarod) and indices of motor unit (MUNE) and muscle (contractility) function. ResultsBeta-hydroxybutyrate (BHB) was significantly higher at 10 weeks in mice on a KD vs control group (0.83 ± 0.44 mmol/l versus 0.42 ± 0.21 mmol/l, η2 = 0.265, unpaired t-test, p = 0.0060). Mice on the KD intervention demonstrated significantly increased hindlimb grip strength (diet, p = 0.0001; time × diet, p = 0.0030), all limb grip strength (diet, p = 0.0005; time × diet, p = 0.0523), and rotarod latency to fall (diet, p = 0.0126; time × diet, p = 0.0021). Mice treated with the KD intervention also demonstrated increased MUNE (diet, p = 0.0465; time × diet, p = 0.0064), but no difference in muscle contractility (diet, p = 0.5248; time × diet, p = 0.5836) or RNS (diet, p = 0.3562; time × diet, p = 0.9871). ConclusionKD intervention improved neuromuscular and motor function in aged mice. This pre-clinical work suggests that further research is needed to assess the efficacy and physiological effects of a KD on indices of sarcopenia.

Correlations of Corneal Endothelial Morphology and Corneal Thickness With Anterior Segment Parameters in Healthy Individuals.

The purpose of this study was to investigate the associations between central corneal endothelial cell density (ECD), endothelial morphology, and corneal thickness (central corneal thickness) with the anterior chamber depth, corneal volume (CV), white-to-white (WTW) distance, mean anterior chamber angle (CAmean), and gender in healthy individuals. This observational study included 136 healthy volunteers. The ECD, coefficient of variation of cell area, and hexagonal cell appearance ratio (%Hex) were measured by means of specular microscopy. The central corneal thickness, anterior chamber depth, CV, WTW distance, and the angle width of 12 points were taken by the Pentacam HR Scheimpflug anterior segment imaging. The arithmetical mean of the 12 points was considered as the CAmean. We used mixed effect linear regression model for the statistical analysis of the data. ECD was positively correlated with CV ( P = 0.028), while after adjusting for age, it was negatively correlated with age ( P < 0.001). Coefficient of variation of cell area was positively correlated with CAmean ( P = 0.036), while after adjusting for age, it was positively correlated with age ( P < 0.001) and CAmean ( P = 0.005). Hex was negatively correlated with WTW ( P = 0.023) and CAmean ( P = 0.025), and after adjusting for age, this correlation remained the same ( P = 0.029 when correlated with WTW and P = 0.035 with CAmean). There were significant changes in the morphology of the corneal endothelial cells in eyes with wider anterior chamber angle. Greater pleomorphism and polymegethism of the corneal endothelium was observed in healthy patients with wider CAmean. Deepening of the anterior chamber as myopia progresses could render the corneal endothelium more fragile and susceptible to mechanical stress, which is an area worthy of further study.

Longitudinal study of change in CD4+ cell counts on HIV-Positive patients at Dalhatu Araf Specialist Hospital, Lafia

The aim of this study was the Longitudinal Study of Change in CD4+ Cell Counts on HIV-Positive Patients at Dalhatu Araf Specialist Hospital, Lafia. The study deployed linear mixed effects models to check if the mean response CD4+ cell count varies with time. The study also attempted to test if the mean response varies in the two groups. An attempt to estimate the relationship between the response and observations according to gender. The study revealed that the trajectory of the mean response over time has a very high variability where we see that there is a general rise in the CD4+ cell counts at the initiation of ART. It was further seen that the CD4+ cell counts in male patients is observed to be higher with higher median value after the sixth observation. A linear mixed effect model was used and tested where it was noted that there is evidence of between-individual heterogeneity which further shows that the decision to choose a mixed effects model instead of an only fixed effects model was in order. The model summary showed that the mean CD4+ cell counts at the baseline (OBS1) was averagely good, but at the initiation of ART, there was a significant increase in the mean response where it was further revealed that the pattern of the mean response over time is not flat. In modelling the group effects, we see the difference between the mean CD4 cell count of male versus female is -113.62 CD4 cell count (i. e. 95% CI= -290.64 to 63.39) lower than female, adjusting with time. Finally, the Wald test does not show any significant evidence of interaction between the observations and gender (p=0.2925) which suggests that the mean response based on gender may be parallel.

The impact of major depressive disorder on glycaemic control in type 2 diabetes: a longitudinal cohort study using UK Biobank primary care records

BackgroundThis study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses.MethodsIn UK Biobank, T2D was defined using self-report and linked health outcome data, then validated using polygenic scores. Repeated HbA1c measurements (mmol/mol) over the 10 years following T2D diagnosis were outcomes in mixed effects models, with disease duration included using restricted cubic splines. Four MDD exposures were considered: MDD diagnosis prior to T2D diagnosis (pre-T2D MDD), time between pre-T2D MDD diagnosis and T2D, new MDD diagnosis during follow-up (post-T2D MDD) and time since post-T2D MDD diagnosis. Models with and without covariate adjustment were considered.ResultsT2D diagnostic criteria were robustly associated with T2D polygenic scores. In 11,837 T2D cases (6.9 years median follow-up), pre-T2D MDD was associated with a 0.92 increase in HbA1c (95% CI: [0.00, 1.84]), but earlier pre-T2D MDD diagnosis correlated with lower HbA1c. These pre-T2D MDD effects became non-significant after covariate adjustment. Post-T2D MDD individuals demonstrated increasing HbA1c with years since MDD diagnosis (β=0.51\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta =0.51$$\\end{document}, 95% CI: [0.17, 0.86]). Retrospectively, across study follow-up, within-patient variability in HbA1c was 1.16 (95% CI: 1.13–1.19) times higher in post-T2D MDD individuals.ConclusionsThe timing of MDD diagnosis is important for understanding glycaemic control in T2D. Poorer control was observed in MDD diagnosed post-T2D, highlighting the importance of depression screening in T2D, and closer monitoring for individuals who develop MDD after T2D.

Relationship between skeletal mitochondrial function and digital markers of free-living physical activity in older adults.

This study examined the association between in vivo skeletal mitochondrial function and digital free-living physical activity patterns-a measure that summarizes biological, phenotypic, functional, and environmental effects on mobility. Among 459 participants (mean age 68years; 55% women) in the Baltimore Longitudinal Study of Aging, mitochondrial function was quantified as skeletal muscle oxidative capacity via post-exercise phosphocreatine recovery rate (τPCr) in the vastus lateralis muscle of the left thigh, using 31P magnetic resonance spectroscopy. Accelerometry was collected using a 7-day, 24-h wrist-worn protocol and summarized into activity amount, intensity, endurance, and accumulation patterning metrics. Linear regression, two-part linear and logistic (bout analyses), and linear mixed effects models (time-of-day analyses) were used to estimate associations between τPCr and each physical activity metric. Interactions by age, sex, and gait speed were tested. After covariate adjustment, higher τPCr (or poorer mitochondrial function) was associated with lower activity counts/day (β = - 6593.7, SE = 2406.0; p = 0.006) and activity intensity (- 81.5 counts, SE = 12.9; p < 0.001). For activity intensity, the magnitude of association was greater for men and those with slower gait speed (interaction p < 0.02 for both). Conversely, τPCr was not associated with daily active minutes/day (p = 0.15), activity fragmentation (p = 0.13), or endurance at any bout length (p > 0.05 for all). Time-of-day analyses show participants with high τPCr were less active from 6:00 a.m. to 12:00 a.m. than those with low τPCr. Results indicate that poorer skeletal mitochondrial function is primarily associated with lower engagement in high intensity activities. Our findings help define the connection between laboratory-measured mitochondrial function and real-world physical activity behavior.

Global climate modeling of the Jupiter troposphere and effect of dry and moist convection on jets

The atmosphere of Jupiter is characterized by banded jets, including an equatorial super-rotating jet, by an intense moist convective activity, and by perturbations exerted by vortices, waves, and turbulence. Even after space exploration missions to Jupiter and detailed numerical modeling of Jupiter, questions remain about the mechanisms underlying the banded jets and the role played by dry and moist convection in maintaining these jets. We report three-dimensional simulations of the Jupiter weather layer using a global climate model (GCM) called Jupiter-DYNAMICO, which couples hydrodynamical integrations on an icosahedral grid with detailed radiative transfer computations. We added a thermal plume model for Jupiter that emulates the effect of mixing of heat, momentum, and tracers by dry and moist convective plumes that are left unresolved in the GCM mesh spacing with a physics-based approach. Our Jupiter-DYNAMICO global climate simulations show that the large-scale Jovian flow, in particular the jet structure, could be highly sensitive to the water abundance in the troposphere and that an abundance threshold exists at which equatorial super-rotation develops. In contrast to our dry (or weakly moist) simulations, simulations that include the observed amount of tropospheric water exhibit a clear-cut super-rotating eastward jet at the equator and a dozen eastward mid-latitude jets that do not migrate poleward. The magnitudes agree with the observations. The convective activity simulated by our thermal plume model is weaker in the equatorial regions than in mid to high latitudes, as indicated by lightning observations. Regardless of whether they are dry or moist, our simulations exhibit the observed inverse energy cascade from small (eddies) to large scales (jets) in a zonostrophic regime.

Chronotropic Incompetence among People with HIV Improves with Exercise Training in the Exercise for Healthy Aging Study.

People with HIV (PWH) have lower exercise capacity compared to peers without HIV, which may be explained by chronotropic incompetence (CI), the inability to increase heart rate during exercise. The Exercise for Healthy Aging Study included adults ages 50-75 with and without HIV. Participants completed 12 weeks of moderate intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; CI <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models. Among 32 PWH and 37 controls (median age 56, 7% female, mean BMI 28 kg/m2), 28% of PWH compared to 11% of controls had CI at baseline (p = 0.067). AHRR was lower among PWH (91 vs 101%; difference 10%, 95% CI 1.9-18.9; p = 0.02). At week 12, AHRR normalized among PWH (+8%, 95% CI 4-11; p < 0.001) and was sustained at week 24 (+5, 95%CI 1-9; p = 0.008) compared to no change among controls (95%CI -4 to 4; p = 0.95; pinteraction = 0.004). After 24 weeks of exercise, only 15% PWH and 10% of controls had CI (p = 0.70). Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training.

Changes in peripheral oxytocin and vasopressin during a silent month-long Insight meditation retreat

BackgroundGiven its putative roles in mediating prosocial behavior, attachment bonds, and stress physiology, oxytocin modulation has been hypothesized to be a biological correlate of the salubrious effects of meditation practice. Here we investigated the effects of a month-long silent meditation retreat on changes in oxytocin, and the related hormone and vasopressin, in relation to psychosocial changes in attachment style, anxiety, personality measures, and feelings of social connectedness with fellow meditators.MethodsPlasma oxytocin and vasopressin and self-report questionnaires were measured in retreat participants (n = 28) at the beginning of, and 3 weeks into, a residential meditation retreat. Control participants (n = 34), who were similar in age, gender, and meditation experience, were also assessed across a 3-week interval. Linear mixed effects models were used to assess outcomes.ResultsThe retreat group showed a small but significant decrease in oxytocin compared to controls who showed no change. In the retreat group, higher openness to experience at Time 1 predicted greater reductions in oxytocin during the retreat, and lower oxytocin at Time 2 was related to stronger feelings of personal connection with fellow meditators. The changes in oxytocin were not related to attachment style or anxiety. Vasopressin decreased over time across both groups, suggesting no specific effect of retreat.ConclusionThese preliminary findings suggest that meditation training in the context of a silent residential retreat may reduce circulating levels of oxytocin. We interpret this finding from multiple theoretical perspectives, discussing key measurement limitations and proposing future study designs that may help to differentiate the effects of different meditation practices and contexts on oxytocin signaling.

A Prospective Cohort Study of Persistent Endocrine Disrupting Chemicals and Perceived Stress.

Persistent endocrine disrupting chemicals (EDCs) can dysregulate the stress response. We evaluated associations between persistent EDCs and perceived stress among participants from the Study of Environment, Lifestyle and Fibroids (n=1,394), a prospective cohort study of Black women. Participants completed the Perceived Stress Scale (PSS-4) at baseline, and every 20 months through 60 months (range of scores: 0-16); higher scores indicated higher stress. EDCs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides, were quantified in plasma samples at baseline. We fit Bayesian Kernel Machine Regression (BKMR) and linear mixed effects models to estimate associations of EDCs (as a mixture and individually) with PSS-4 scores at baseline and at each follow-up visit, respectively. Increasing percentiles of the mixture were not strongly associated with PSS-4 scores at baseline, and no interactions were observed among EDCs. Several individual EDCs (e.g., PFDA, PCB 118, PBDE 99) were associated with higher PSS-4 scores at baseline or follow-up, while other EDCs (e.g., PCB 138/158) were associated with lower PSS-4 scores at baseline or follow-up. The directionality of associations for individual EDCs was inconsistent across follow-up visits. In conclusion, specific EDCs may be associated with perceived stress in Black women.

The characteristics of brain atrophy prior to the onset of Alzheimer’s disease: a longitudinal study

ObjectiveWe aimed to use the onset time of Alzheimer’s disease (AD) as the reference time to longitudinally investigate the atrophic characteristics of brain structures prior to the onset of AD.Materials and methodsA total of 328 participants from the ADNI database with clear onset of AD and structural imaging data were included in our study. The time before the onset of AD (abbreviated as BAD) was calculated. We investigated the longitudinal brain changes in 97 regions using multivariate linear mixed effects regression models.ResultsThe average BAD was −28.15 months, with a range from −156 to 0 months. The 54 brain regions showed significant atrophy prior to the onset of AD, and these regions were mainly distributed in the frontal and temporal lobes. The parietal and occipital lobe exhibited relatively less atrophy than the other brain lobes. Sex, age, and magnetic field strength had greater direct impacts on structural indicators than APOE genotype and education. The analysis of interaction effects revealed that the APOE ε4 mutation carriers exhibited more severe structural changes in specific brain regions as the BAD increased. However, sex, age, and education had minimal regulatory influence on the structural changes associated with BAD.ConclusionLongitudinal analysis, with the onset time point of AD as the reference, can accurately describe the features of structural changes preceding the onset of AD and provide a comprehensive understanding of AD development.

Educational telerehabilitation program for women with pelvic floor dysfunctions after gynecological pelvic cancer treatment: protocol study for a randomized and controlled clinical trial

BackgroundEducational and self-care measures are important for women after gynecological pelvic cancer treatment. Pelvic floor muscle training exercises (PFMT) are a conservative treatment for pelvic floor (PF) dysfunction. The purpose is to evaluate the impact of a telerehabilitation and self-care program on PF dysfunctions, reports of urinary incontinence (UI), and physical–emotional factors of participants post-treatment for gynecological pelvic cancer.MethodsTwo-arm randomized clinical trial: an intervention group (IG) will evaluate the effect of a telerehabilitation program on women undergoing clinical practice of radiotherapy for the treatment of gynecological pelvic cancer and a control group (CG) will maintain the routine. Primary outcome is the prevalence of reports of UI, which will be assessed using the International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF). The secondary outcomes will be the severity and impact of UI on quality of life, location and perception of pain intensity, presence and intensity of dyspareunia, vaginal stenosis, fecal incontinence (FI), and levels of physical activity. Statistical analysis will be performed by intention-to-treat, and multivariate mixed effects analysis will be used to compare results.DiscussionActivities in the context of telerehabilitation using PFMT and self-care can represent a viable and effective solution to minimize the side effects of gynecological cancer treatment and improve women’s quality of life.

Evaluation of warm mix effect in laboratory using a self-developed WMA additive Alube

In response to the problems of high mixing temperatures and energy consumption of polymer-modified asphalt mixtures in road construction, a surfactant-based warm mix additive ‘Alube’ was developed. The warm mix SBS-modified asphalt and its mixture were prepared. Their rheological performance and chemical structure were analysed by the rheological and microscopic tests. The active mixing power (P) of asphalt mixtures were examined by the variable speed mixing (VSM) test. The mixing flowability model was then established to evaluate the warm mix effect. The results indicated that the mixing flowability of asphalt mixtures obeyed the linear Bingham visco-plastic model, and the slope and intercept of the flow straight characterised the mixing viscosity and plastic limit. It is evaluated that 0.7% Alube1 and Evotherm reduced the mixing temperature of SBS-modified asphalt mixture by 14°C and 12°C, respectively. Moreover, Alube1 is suitable for a wide range of applications through warm mix asphalt technology.

The U-shaped relationship between corruption and international tourism demand: A gravity model approach

The tourism industry significantly contributes to a country’s economic growth and creates a positive image of the destination. This study assesses the impact of corruption on international tourism demand. It employs two-dimensional analyses using the gravity model and a pooled ordinary least square estimator to provide a unique recognition of international tourism demand. The study utilized a conditional quantile regression technique to analyze a dataset of 200 destination countries from 1995 to 2022. The empirical results demonstrate a mixed effect of corruption on international tourism demand. The analysis reveals a non-linear relationship between corruption and international tourism demand, with the inverted-U relationship being statistically significant only at the 50th–75th quantiles and not holding at the upper and lower quantiles. The research confirms that income has a positive impact on tourism across quantiles, but the impact is disproportionate. The sub-period of 2006–2022 experienced a significant decline in gross domestic product (GDP) due to the global financial crisis and its aftershocks, which severely impacted the attractiveness of destination countries for tourists. These valuable insights can inform national tourism policies and businesses.

The effect of antipsychotic medications on QTc and delirium in paediatric cardiac patients with ICU delirium.

Children with prolonged hospital admissions for CHD often develop delirium. Antipsychotic medications (APMs) have been used to treat delirium but are known to prolong the QTc duration. There is concern for prolongation of the QTc interval in cardiac patients who may be more vulnerable to electrocardiogram (ECG) changes and may have postoperative QTc prolongation already. The goal of this study was to determine the effect of APM on QTc duration in postoperative paediatric cardiac patients and determine the effect of quetiapine and risperidone in treating delirium and QTc prolongation. Retrospective study, July 1, 2017-May 31, 2022. Tertiary children's hospital. Included were patients admitted to the paediatric cardiac ICU at Children's Healthcare of Atlanta. None. ECGs, delirium scores, and drug information were collected. Delirium was defined as Cornell Assessment of Pediatric Delirium (CAPD) score >9. Mixed effect models were performed to evaluate the effect of surgery on QTc change and the effect of antipsychotics on QTc and CAPD changes. There were 139 children, 55% male and 67% surgical admissions. Median age was 5.9 months. Mean QTc increased after cardiac surgery by 18 ms (p = 0.014, 95% CI 3.65-32.4). There was no significant change in QTc after antipsychotic administration (p = 0.064). The mean CAPD score decreased (12.5-7.2; p < 0.001). Quetiapine had the most improvement in delirium, and risperidone had the least improvement (77.8%, n = 14; 37.8%, n = 34, respectively; p = 0.002). The QTc interval did not have a statistically significant change after the administration of antipsychotics, while there was improvement in the CAPD score. APMs may be administered safely without significant prolongation of the QTc and are an effective treatment for delirium.

Archetypes of influential users in social question-answering sites

PurposeThis paper seeks to address the following two research questions. RQ1: What are the influential user archetypes in the social question-answering (SQA) community? RQ2: To what extent does user feedback affect influential users in changing from one archetype to another?Design/methodology/approachBased on a sample of 13,840 influential users drawn from the Covid-19 community on Zhihu, the archetypes of influential users were derived from their ongoing participation behavior in the community using the Gaussian mixture model. Additionally, user feedback characteristics such as relevance and volume from 222,965 commenters who contributed 546,344 comments were analyzed using the multinomial logistic regression model to investigate the archetype change of influential users.FindingsFindings suggest that influential users could be clustered into three distinctive archetypes: touch-and-go influential users, proactive influential users and super influential users. Moreover, feedback variables have various impacts on the influential user archetype change, including a shift toward creating higher-quality content and fostering increased interaction, a shift toward generating lower-quality content and decreased interaction but improved speed and having mixed effects due to differences in information processing among these archetypes.Originality/valueThis study expands the existing knowledge of influential users and proposes practical approaches to cultivate them further.

GR.3 Distinct longitudinal brain atrophy trajectories in parkinson’s disease clinical subtypes: insight towards precision medicine

Background: Parkinson’s disease (PD) varies widely across individuals in terms of clinical manifestations and course of progression. We aimed to compare patterns of brain atrophy between PD clinical subtypes using longitudinally acquired brain MRIs. Methods: We used T1-weighted MRIs from Parkinson’s Progression Markers Initiative (PPMI) on 134 PD individuals and 60 healthy controls with at least two MRIs. Patients were classified into three clinical subtypes at de novo stage using validated subtyping criteria based on major motor and non-motor classifiers (early cognitive impairment, RBD, dysautonomia): mild-motor predominant (n=74), intermediate (n=44), and diffuse-malignant (n=16). Deformation-based morphometry (DBM) maps were calculated and mixed effect models were used to examine the interaction between PD subtypes and rate of atrophy across brain regions over time, controlling for sex and age at baseline. Results: Individuals with ‘diffuse malignant’ PD showed a significantly higher rate of atrophy across multiple brain regions, including lateral nucleus of the forebrain, precuneus, paracentral lobule, inferior temporal gyrus, fusiform gyrus, and lateral hemisphere of the cerebellum (FDR corrected p&lt;0.05). Conclusions: We demonstrated an accelerated atrophy pattern within several brain regions in ‘diffuse malignant’ PD subtype. These findings suggest the presence of a more diffuse multidomain neurodegenerative process in a subgroup of people with PD, favoring the existence of diverse underlying pathophysiologies.

Prolonged intermittent theta burst stimulation targeting the left prefrontal cortex and cerebellum does not affect executive functions in healthy individuals

Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.

Access to drinking safe water and its associated factors among households in East Africa: a mixed effect analysis using 12 East African countries recent national health survey

BackgroundMore than half of the population in Sub-Saharan Africa (SSA) faces limited access to safe drinking water. Unimproved water sources can pose risks to the health of entire households, particularly women and children. Despite the fact that East African countries have some of the poorest drinking water infrastructures globally, there is a lack of published data on this issue. Consequently, the objective of this study was to examine access to safe drinking water and its determinants among households in East Africa, utilizing recent nationally representative data.MethodsThis study analyzed data from recent demographic and health surveys conducted in 12 East African nations between 2011 and 2022. Data were gathered from 204,275 households. A stratified two-stage cluster sampling method was employed, with enumeration areas serving as the main sampling units and households serving as the secondary sampling units. Binary and multiple multilevel logistic regression were used to examine the relevant factors associated with the use of different sources of drinking water in the region. In binary regression and multiple regression, P values of ≤ 0.2 and < 0.05, respectively, were used to determine the statistical significance of variables in the final model.ResultsApproximately 72.62% (95% CI = 72.43, 72.83) of households have utilized improved sources of drinking water. Household heads aged 25–35 years (AOR = 1.09, 95% CI = 1.04, 1.14), 36–45 years (AOR = 1.09, 95% CI = 1.04, 1.14), and > 45 years (AOR = 1.08, 95% CI = 1.04, 1.14), those with secondary/higher education (AOR = 1.24, 95% CI = 1.20–1.29), and individuals in wealth index categories of poorest (AOR = 0.17, 95% CI = 0.16, 0.18), poorer (AOR = 0.21, 95% CI = 0.19, 0.22), middle (AOR = 0.25, 95% CI = 0.24, 0.27), and richer (AOR = 0.36, 95% CI = 0.34, 0.38) were associated with improved sources of drinking water. Additionally, female household leaders (AOR = 1.23, 95% CI = 1.20, 1.26), > 30 min of time taken to access the water source (AOR = 2.00, 95% CI = 1.95, 2.05), improved toilet facilities (AOR = 2.25, 95% CI = 2.19, 2.31), rural residence (AOR = 0.43, 95% CI = 0.42, 0.45), high community wealth (AOR = 1.31, 95% CI = 1.13–1.51), community media exposure (AOR = 1.32, 95% CI = 1.15, 1.51) were associated with improved sources of drinking water, respectively.ConclusionApproximately three-quarters of the population in East Africa has access to improved drinking water, although the quality of water in the region is still considered poor. It is important for relevant organizations to collaborate in order to improve the quality of drinking water, with special attention given to high-risk groups such as communities with high poverty and low literacy rates, poor households, and rural residents. Strengthening women’s empowerment and increasing mass media exposure can also play a crucial role in accelerating the adoption of improved drinking water sources in East Africa.